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Updated: Oct 1, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
High-Content Screening Pipeline for Natural Products Targeting Oncogenic Signaling in Melanoma
Lara Dürr1, Tanja Hell1, Maciej Dobrzyński2
1Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Abstract:
The incidence of melanoma, the most fatal dermatological cancer, has dramatically increased over the last few decades. Modern targeted therapy with kinase inhibitors induces potent clinical responses, but drug resistance quickly develops. Combination therapy improves treatment outcomes. Therefore, novel inhibitors targeting aberrant proliferative signaling in melanoma via the MAPK/ERK and PI3K/AKT pathways are urgently needed. Biosensors were combined that report on ERK/AKT activity with image-based high-content screening and HPLC-based activity profiling. An in-house library of 2576 plant extracts was screened on two melanoma cell lines with different oncogenic mutations leading to pathological ERK/AKT activity. Out of 140 plant extract hits, 44 were selected for HPLC activity profiling. Active thymol derivatives and piperamides from Arnica montana and Piper nigrum were identified that inhibited pathological ERK and/or AKT activity. The pipeline used enabled an efficient identification of natural products targeting oncogenic signaling in melanoma.
Insights
Researchers identified natural compounds from plants like Arnica montana and Piper nigrum that inhibit key signaling pathways in melanoma. This discovery offers potential for new combination therapies against drug-resistant skin cancer.
Area of Science:
- Dermatology and Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Melanoma incidence is rising, and current targeted therapies face rapid drug resistance.
- Aberrant MAPK/ERK and PI3K/AKT signaling pathways drive melanoma proliferation.
- Novel therapeutic strategies, including combination therapies, are crucial for effective melanoma treatment.
Purpose of the Study:
- To identify novel natural product inhibitors targeting oncogenic signaling pathways in melanoma.
- To screen a library of plant extracts for compounds that modulate ERK/AKT activity.
- To develop an efficient pipeline for discovering natural products against melanoma.
Main Methods:
- Utilized biosensors to monitor ERK/AKT activity in melanoma cell lines.
- Employed image-based high-content screening of 2576 plant extracts.
- Conducted HPLC-based activity profiling on selected plant extract hits.
Main Results:
- Identified 140 plant extract hits, with 44 selected for further profiling.
- Discovered active thymol derivatives and piperamides from Arnica montana and Piper nigrum.
- These compounds demonstrated inhibition of pathological ERK and/or AKT activity.
Conclusions:
- The developed screening pipeline efficiently identifies natural products targeting melanoma signaling.
- Arnica montana and Piper nigrum yield compounds with potential anti-melanoma activity.
- Natural products offer a promising avenue for developing new melanoma therapies.
